Outcome of catheter ablation in the very elderly-insights from a large matched analysis

BackgroundAblation emerged as first line therapy in the treatment of various arrhythmias. Nevertheless, in older patients (pts), decision is often made pro drug treatment as more complications and less benefit are suspected.HypothesisWe hypothesized that different kind of ablations can be performed safely regardless of the pts age.MethodsWe enrolled all pts aged >80 years (yrs) who underwent ablation for three different arrhythmias (atrial flutter [AFL], atrioventricular nodal re‐entry tachycardia [AVNRT], ventricular tachycardia [VT]) between August 2002 and December 2018. Procedural data and outcome were compared with matched groups aged 60 to 80 years and 40 to 60 years, respectively. Periprocedural and in‐hospital complications were analyzed.ResultsThe analysis included 1191 patients (397 pts per group: 63% AFL, 23% AVNRT, 14% VT) who underwent ablation. Acute success was high in all types of arrhythmias irrespective of age (>80, 60‐80, 40‐60 years: AFL 97%/98%/98%, AVNRT 97%/95%/97%, VT 82%/86%/93%). Rate of periprocedural complications were similar in all groups treated for AFL and AVNRT. For VT ablations significant differences were noted between pts > 80 or 60 to 80 years and those aged 40‐60 years (16.1%/14.3%/3.6%). Most complications were infections and groin haematoma. No strokes, iatrogenic atrioventricular blocks and deaths related to the ablation occurred.ConclusionAblation appears safe in pts > 80 years. Success rates were comparable to matched younger cohorts. A significant difference was observed for VT patients.     

Differential impact of belatacept and cyclosporine A on central aortic blood pressure and arterial stiffness after renal transplantation

Calcineurin inhibitors (CNI) are potent vasoconstrictors and induce an acceleration of arteriosclerosis, thus contributing to the cardiovascular risk after renal transplantation. The study compares the impact of belatacept and cyclosporine A (CsA) on arterial stiffness and central aortic blood pressure. We performed a case–control study in 46 patients (23 on belatacept and 23 on CsA) matched for age, body mass index, time after transplantation, and time on dialysis prior to transplantation. Pulse wave analysis (SphygmoCor, AtCor^®) was used to assess central aortic blood pressure, aortic augmentation pressure, and pulse wave velocity (PWV) as a marker of arterial stiffness. Assessment of vascular function was performed after a minimum of 20 months and a median follow‐up of 81 months post‐transplant. Peripheral systolic and diastolic blood pressure did not significantly differ in the two groups (p > 0.05 each). The central aortic augmentation pressure was higher in the CsA group (12.7 mmHg vs. 7.3 mmHg, p = 0.048). PWV as a measure of arterial stiffness did not differ in the two groups. Thus, belatacept is not associated with a significant difference in arterial stiffness compared to CsA after a median of 81 months post‐transplant. It is associated, however, with a lower aortic augmentation pressure, a strong independent cardiovascular risk factor.     

Phenotype and function of human B cells expressing CD70 (CD27 ligand)

CD70, the cellular ligand of the tumor necrosis factor receptor family member CD27, can be found on a limited number of germinal center (GC) B cells in some tonsils, on scattered lymphocytes residing in secondary lymphoid organs, and on a fraction of the circulating B cell population. Due to the restricted expression of CD70 in vivo, we analyzed signals that determine CD70 expression levels and characterized the phenotype and function of CD70⁺ B cells. Expression of CD70 on B cells activated in vitro was found to be dependent on the continuous presence of a B cell antigen receptor cross-linking agent, and induced or potentiated by CD40 ligation but was down-modulated by the Th2 cytokines interleukin (IL)-4 and IL-13. Both in peripheral blood and tonsil cell suspensions, CD70⁺ B cell subpopulations were found to be enriched for CD27-and IgG-expressing cells, but contained less IgD⁺ B cells. Additional analysis of markers which define specific differentiation stages (Bm1-5) of mature B cells within human tonsils did not place CD70-expressing B cells in one of these subsets. Functional experiments revealed that whereas both CD70⁻ and CD70⁺ B cells can secrete immunoglobulin after activation with a combination of Staphylococcus aureus Cowan strain I and IL-2, only CD70⁺ B cells can produce large quantities of antibodies when stimulated in a T cell-dependent fashion. Our combined data imply that CD70 is a marker for mature B cells which have recently been primed by antigen in vivo.     

The intrinsic piezoelectric properties of materials – a review with a focus on biological materials

Piezoelectricity, a linear electromechanical coupling, is of great interest due to its extensive applications including energy harvesters, biomedical, sensors, and automobiles. A growing amount of research has been done to investigate the energy harvesting potential of this phenomenon. Traditional piezoelectric inorganics show high piezoelectric outputs but are often brittle, inflexible and may contain toxic compounds such as lead. On the other hand, biological piezoelectric materials are biodegradable, biocompatible, abundant, low in toxicity and are easy to fabricate. Thus, they are useful for many applications such as tissue engineering, biomedical and energy harvesting. This paper attempts to explain the basis of piezoelectricity in biological and non-biological materials and research involved in those materials as well as applications and limitations of each type of piezoelectric material.

Piezoelectricity, a linear electromechanical coupling, is of great interest due to its extensive applications including energy harvesters, biomedical, sensors, and automobiles.     

Biperiden and mepazine effectively inhibit MALT1 activity and tumor growth in pancreatic cancer

MALT1 is a key mediator of NF-κB signaling and a main driver of B-cell lymphomas. Remarkably, MALT1 is expressed in the majority of pancreatic ductal adenocarcinomas (PDACs) as well, but absent from normal exocrine pancreatic tissue. Following, MALT1 shows off to be a specific target in cancer cells of PDAC without affecting regular pancreatic cells. Therefore, we studied the impact of pharmacological MALT1 inhibition in pancreatic cancer and showed promising effects on tumor progression. Mepazine (Mep), a phenothiazine derivative, is a known potent MALT1 inhibitor. Newly, we described that biperiden (Bip) is a potent MALT1 inhibitor with even less pharmacological side effects. Thus, Bip is a promising drug leading to reduced proliferation and increased apoptosis in PDAC cells in vitro and in vivo. By compromising MALT1 activity, nuclear translocation of c-Rel is prevented. c-Rel is critical for NF-κB-dependent inhibition of apoptosis. Hence, off-label use of Bip or Mep represents a promising new therapeutic approach to PDAC treatment. Regularly, the Anticholinergicum Bip is used to treat neurological side effects of Phenothiazines, like extrapyramidal symptoms.     

Structure of the human tibialis posterior tendon

Background The most common site of rupture of the posterior tibial tendon is the retromalleolar region where the tendon changes its direction of pull. The aim of this study was to characterize the tissue of the gliding zone of the tibialis posterior tendon to gain further knowledge about possible structural causes for spontaneous tendon rupture. Methods Light microscopy, transmission electron microscopy and immunohistochemical methods were used to describe the structure of the human tibialis posterior tendon. Results In the region where the tendon wraps around the medial malleolus, the structure of the tissue changes from the typical structure of a traction tendon. The superficial zone which was directed towards the pulley tissue had the structure of fibrocartilage with a specific three-dimensional collagen fibril texture. Transmission electron microscopy showed chondrocytes with a felt-like pericellular matrix that increased in size towards the gliding surface. The extracellular matrix of the fibrocartilage was rich in acid glycosaminoglycans and stained intensively with alcian blue at pH 1. Immunohistochemical staining of cartilage-specific extracellular matrix components such as type II collagen, chondroitin-4-sulphate, chondroitin-6-sulphate, keratan sulphate and aggrecan was positive. Conclusion The location of the fibrocartilage corresponds to the region where the tibialis posterior tendon wraps around the medial malleolus, which serves as a pulley. According to the theory of 'causal histogenesis', the stimulus for the development of fibrocartilage within dense connective tissue is intermittent compressive and shear stress. The fibrocartilaginous region is the region where most spontaneous ruptures of the tibialis posterior tendon occur. Due to its structure, the fibrocartilaginous region may be more vulnerable to repetitive tensile microtrauma; degeneration may occur due to the poor repair response of the avascular fibrocartilaginous tissue.